Acute ('binge") doses of ethanol administered to pregnant C57B1/6J mice on gestational day 8 1/2 (at the time of neural crest cell migration) lead to major malformations of the face, thymus and heart. Preliminary observations utilizing scanning electron microscopy (SEM) and light microscopy (LM) demonstrate marked cellular necrosis in specific cell populations including cranial neural crest cells. cells in the otic placodes and in the sensory ganglionic placodes and contiguous closing membranes. These bilaminar (pharyngeal endoderm and surface ectoderm) closing membranes separate visceral pouches and clefts in their proximal regions. Few other structures appear to be initially affected. The resulting malformations are similar to those seen in the human DiGeorge syndrome and CHARGE association. This application would permit completion of pilot studies necessary for the design of more detailed experiments. Observations to be made include further SEM observations and much additional study at the LM level. For the latter, the fixation and staining methods used by Nichols to enhance distinction of neural crest cells will be tested. Where indicated, selected areas will be studied by transmission EM. The period covered by these studies will be gestational day 8 1/2 through 11 1/4. Structures examined will include neural crest, placodes, brain, eye, pharyngeal glands and heart. Mitotic indices will be calculated for many of these tissues from day 8 3/4 to 9 3/4. Further studies would include a more detailed study of growth alterations, more careful examination of migrating crest and placodal cells, stages at which pharyngela gland development is affected, etc. Examination of direct effects of ethanol (and acetaldehyde?) on embryos developing in culture should be very fruitful because of the ease of growing embryos at this stage and the apparent specificity of in vivo effects. Explanted crest cells should make an excellent model for following the effects of ethanol on a migrating cell population.